Advertisement
Advertisement

AIDS 2004; Bangkok, Thailand; July 11-16, 2004

Key Links:

By Topic:

Search:



See Also
Advertisement:
View week 96 data from a head-to-head study comparing two HIV-1 single-tablet regimens >

UNBP0518 04/14

The Body PRO Covers: The XV International AIDS Conference

HDL Benefit Is Maintained With Extension of Nevirapine and Efavirenz Treatment in 2NN Study

July 14, 2004

Background

Since the large prospective D:A:D (Data Collection on Adverse Events of Anti-HIV Drugs) study linked duration of antiretroviral therapy to a higher risk of myocardial infarction,1 there has been new attention paid to the impact of highly active antiretroviral therapy (HAART) on lipid levels. As a result of the emerging data on adverse metabolic effects associated with these agents, experienced HIV providers now take the metabolic and lipid effects of these agents into consideration when prescribing antiretroviral therapy.

Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART, particularly nevirapine (NVP, Viramune), has been shown to increase high-density lipoprotein (HDL) cholesterol levels, sometimes quite considerably.2 The 2NN study compared nevirapine and efavirenz (EFV, Sustiva, Stocrin)-based therapy in 1,216 treatment-naive patients. Both groups received background therapy with stavudine (d4T, Zerit) and lamivudine (3TC, Epivir), and were followed for 48 weeks. There were increases in HDL cholesterol observed in both groups, but the nevirapine-treated subjects had significantly greater HDL increases than those treated with efavirenz.3

The 2NN Extension Trial

One of the criticisms leveled at the 2NN study was that a 48-week follow-up was too short a period of time to fully assess the efficacy and metabolic effects of antiretroviral therapy. The purpose of this analysis was to provide longer-term data on the lipid changes, and to see whether the differences between nevirapine and efavirenz would persist.

This study was a single cross-sectional analysis of fasting blood samples from patients who were still on their original randomized NNRTI treatment after completion of the trial. Because enrollment in this study occurred over a period of 16 months, there was considerable variation in the length of time on antiretroviral therapy when the lipid analysis was performed.

At the 48-week mark in the 2NN trial, there were 417 subjects on nevirapine, with 178 available for the extension lipid testing. Similarly, there were 289 subjects on efavirenz and 123 available for fasting lipid analysis. The post-trial samples for this study were performed at a median of 84 weeks (range 48-132 weeks) after initiation of antiretroviral therapy.

Both the nevirapine and efavirenz groups continued to show increases in HDL at the post-treatment time points, as this table indicates.


NVP (n = 178)
 BaseW48PT
HDL-cholesterol1.014734
LDL-cholesterol2.283365
Total cholesterol3.962845
Triglycerides1.612095
EFV (n = 123)
 BaseW48PT
HDL-cholesterol1.053731
LDL-cholesterol2.356072
Total cholesterol4.033545
Triglycerides1.4842126
Base = baseline; W48 = % increase start ART med week 48; PT = % increase start ART and post-trial time point


However, the significant difference between HDL levels in the nevirapine and efavirenz groups that was present at week 48 was no longer present at the post-treatment time point.


HDL Benefit Is Maintained With Extension of Nevirapine and Efavirenz Treatment in 2NN Study


In both groups, the authors observed a significant jump in total cholesterol, low-density lipoprotein cholesterol, and triglycerides at the post-treatment time point.


HDL Benefit Is Maintained With Extension of Nevirapine and Efavirenz Treatment in 2NN Study


HDL Benefit Is Maintained With Extension of Nevirapine and Efavirenz Treatment in 2NN Study


One of the potential explanations proposed was that because 90% of the patients were on stavudine, the deleterious metabolic effects of stavudine may have been driving the lipid increases.

Comment

This follow-up information on the 2NN study was interesting and informative, but the authors acknowledged the limitations inherent in post hoc trial addenda. For example, the extremely high drop-out rate weakened the study, as did the variable time to lipid testing after initiation of HAART.

Actually, the most notable aspect of this data was not that the HDL benefit persisted during the extension, but that the overall cholesterol and triglycerides increased so much in both groups. This finding is probably a reflection of the long-term effects of stavudine use, and the ability of this agent to overcome the potentially beneficial HDL-raising effects of both efavirenz and nevirapine.

These data highlight the importance of longer-term follow-up in contemporary HIV research to more fully elucidate the metabolic effects of long-term antiretroviral therapy.

Footnotes

  1. The Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study Group. Combination antiretroviral therapy and the risk of myocardial infarction. N Engl J Med. November 20, 2003;349(21):1993-2003.

  2. Fisac C, Fumero E, Crespo M, et al. A randomized trial of metabolic and body composition changes in patients switching from PI-containing regimens to abacavir (ABC), efavirenz (EFV) or nevirapine (NVP). In: Program and abstracts of the 9th Conference on Retroviruses and Opportunistic Infections; February 24-28, 2002; Seattle, Wash. Abstract 699.

  3. van Leth F, Phanuphak P, Gazzard B, et al. Lipid changes in a randomized comparative trial of first-line antiretroviral therapy with regimens containing either nevirapine alone, efavirenz alone or both drugs combined, together with stavudine and lamivudine (2NN Study). In: Program and abstracts of the 10th Conference on Retroviruses and Opportunistic Infections; February 10-14, 2003; Boston, Mass. Abstract 752.

Complete Index

Tell us what you think of The Body's conference coverage!

Reference

Abstract: Increase in High-Density Lipoprotein Cholesterol When Using Nevirapine and/or Efavirenz Is Maintained Up to 2 Years (Poster WePpB2065)
Authored by: F van Leth, D Hall, J M A Lange, P Reiss


This article was provided by TheBodyPRO.com. It is a part of the publication The XV International AIDS Conference.
 



Please note: Knowledge about HIV changes rapidly. Note the date of this summary's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this summary. For a complete listing of our most recent conference coverage, click here.
Advertisement